This invention relates to wound cleansing compositions, and particularly to physiologically compatible wound cleansing compositions and wound cleansing concentrates.
Emergency room physicians treat an estimated ten million traumatic wounds each year in the United States. The goal in treating these wounds is to prevent infection, restore function and provide good cosmoses.
Wound healing has been the subject of trials and errors for thousands of years. In treating wounds, people have tried mud packs, honey poultices, fire, dry and moist dressings. Only recently, however, has the underlying molecular process of wound healing been extensively studied. One finding has been that a handful of growth factors play key roles in every step of wound healing--from the response immediately following an injury to bringing the healing process to an orderly close. Another component in would healing is the extracellular matrix. This matrix is a cross-linked structure of proteins and polysaccharides, whose structure organizes the geometry of normal tissue. It is the delicate balance between growth factors and the matrix that is important in every step of wound healing.
Following a cut, fibrinogen, which is a protein circulation in the blood stream, forms a fibrin clot, sealing damaged blood vessels. Fibronectin, another protein in the clot, links up to the matrix, forming a bridge between the clot and the surrounding tissue.
The matrix, however, does more than simply stabilize the clot. Alterations in the matrix caused by injury appear to initiate cellular response, including the release of growth factors. For example, before wounding, basic fibroblast growth factor (bFGF) is tightly bound to the matrix outside normal skin and muscle cells, and probes for the bFGF receptor on the cells' surfaces or for its messenger RNA inside them come up negative.
Soon after any major invasive insult, either a mechanical or chemical injury, this picture changes dramatically. The matrix releases bFGF and signals cells to begin manufacturing that growth factor and expressing its receptor on their surface. Each of the growth factors produced during wound healing causes a variety of cell types to proliferate. Unless the growth factors are confined to the wound, they could stimulate cell division where it is not needed and could actually be harmful. It is the matrix that choreographs this healing process. The matrix functions as a combination "passageway and road sign" system, guiding rapidly moving cells toward the target zone. Thus the cell firs breaks free from its initial position in the matrix, then moves along the matrix toward the wound, and eventually anchors itself again.
For a wound to heal with maximum efficiency, proper cleansing is essential. The purpose of wound cleansing in the management of a wound is to prevent infection and to promote healing of the injured tissue. Wound cleansing is accomplished by removal of contaminating bacteria and debridement of necrotic tissue and foreign materials from the wound.
Wound cleansing and wound disinfection have often been combined. Thus, most manufacturers of wound cleansers have traditionally added some antiseptic reagent, in excess of what is actually needed, to their would cleansing materials. Technically, wound cleansing and would disinfection are two areas of wound management that should be considered as separate components. Each component has a specific purpose. It is acceptable to cleanse the wound first and then, if needed, to disinfect it with an appropriate antiseptic material. Excess disinfectants, regardless of type, cause damage to a tissue and will interfere with tissue function, thus they increase the injury that already exists and, consequently, delay wound healing. The inappropriateness of adding excess disinfectant to a would cleanser is shown by the fact that a wound has an exquisite capability to protect itself against bacterial challenges if its natural defenses are not inhibited.
Cells that are important to wound healing include: (1) Fibroblasts that are going to result in the healing; and (2) the granulocytes and monocytes that are going to clean up and eliminate the bacteria and foreign debris. The monocytes/macrophage system orchestrates all phases of wound healing.
In the management of a wound, one should strive to avoid adding trauma to the injured tissues. By definition, a would is either a physical or a chemical trauma to the body. A wound is a traumatic insult to the integrity of a tissue. Thus, any additional trauma inflicted upon the tissue would simply delay the healing process.
Mechanical trauma is any physical force applied to a tissue and which physical force exceeds the physiological limits of the tissue. Thus, physical trauma includes additional trauma that one imparts to the wound in over zealous attempts to cleanse it by scrubbing with an abrasive material, or the inappropriate removal of adherent dressings.
Chemical trauma occurs when a physiologically incompatible agent is added to a tissue. Thus, chemical trauma includes any non-physiological agent added to a wound.
Commercial wound cleansers consist principally of two parts: An active agent and a carrier. The active ingredients generally possess surface active effects. Unfortunately, the carriers used in many of the commercially available wound cleansers are toxic. Consequently, although the active agents may have physiologic benefits, they do not normally transfer that benefit to the wound because of their innate toxicity and toxicity associated with the carrier. Most commercial products do not balance their efficacy and safety physiochemical profile.
Dakin's solution, a buffered 0.5 percent solution of sodium or potassium hypochlorite, was introduced in World War I as an antiseptic irrigant for a wound. It is now known to be injurious to tissues, and is therefore considered more a debriding agent than a cleansing one. Its antimicrobial action is due to release of hypochlorous acid, which is active in neutral or acidic solutions but is less active in alkaline solutions.
Dilute solutions of quaternary ammonium salts are cationic surface-active agents used to cleanse wounds. But these solutions have the drawback of being effective only on gram-positive microorganisms.
Another cleanser is topical iodophor. The combination of iodine and a solubilizing agent slowly liberates free iodine when diluted with water, and is therefore called an iodophor (iodo-iodine, and phor-carrier). Application of iodophor over large wound surfaces usually results in a substantial increase in free iodine. However, included in the complications of iodophor absorptions are renal failure, metabolic acidosis, and increased serum enzyme levels. One example of iodophor is Betadine.RTM. (Purdue Frederick). It is a surgical scrub solution containing 7.5 percent polyvinylpyrrolidone-iodine with 0.75 percent free iodine and an anionic detergent.
Hydrogen peroxide is commonly used as a wound irrigant. It has little value as an antiseptic and is more effective as a sporicide than a bactericide. However, even low concentrations of hydrogen peroxide are damaging to tissues.
Chlorohexidine is used as a wound irrigant solution because of its antimicrobial activity. Although it has good antibacterial properties, a 0.5 percent solution of chlorhexidine has been found to slow granulation issue formation with prolonged wound contact.
PHisoHex.RTM. (Withrop Laboratories) is an antibacterial sudsing emulsion. It contains a colloidal dispersion of 3 percent (w/v) hexachlorophene in an emulsion consisting of entsufon sodium, petrolatum, lanolin cholesterols, methylcellulose, polyethylene glycol, polyethylene glycol monostearate, lauryl myristyl diethanolamide, sodium benzoate and water. Entsufon sodium, or sodium octylphenoxy-ethoxyethyl ether sulfonate, is a synthetic detergent. Hexachlorophene is active against Gram-positive bacteria, but its effect on Gram-negative bacteria is weak.
Hibiclens.RTM. (Stuart Pharmaceuticals) contains 4 percent chlorhexidine gluconate and 4 percent isopropyl alcohol in a mild sudsing base (poloxamer) adjusted to pH 5.0 to 6.5. Further, it also contains a fragrance. It has activities against both Gram-positive and Gram-negative bacteria.
Shur-Clens.RTM. ()Biosyntec, Inc.) is a skin wound cleanser that has been approved by the Food and Drug Administration for use in man. It contains about 20 percent polyoxamer 188. This polyol contains 80 percent ethylene oxide content by weight with an average molecular weight of 8,350. It is a nonionic detergent that does not display antibacterial activity.
Pluronic F-68 (BASF Wyandotte Corp.) is a new skin wound cleanser that has also been approved by the Food and Drug Administration for use in man. It is a surface-active agent that solubilizes iodine resulting in a Pluronic iodophor. Pluronic F-68 is synthesized by adding propylene oxide to the two hydroxyl groups of a propylene glycol nucleus. To the ends of this hydrophobic base are added hydrophilic ethylene oxide units. In the case of Pluronic F-68, the hydrophilic groups are controlled in length to constitute 80 percent of the final molecule.
U.S. Pat. No. 4,708,873 to Schulte describes a composition adapted for application to the skin consisting of a solution of biphenamine in aloe vera. The solution is used to promote debridement of necrotic tissue from an abnormal, ulcerated necrotic tissue on sin or mucous membrane of a patient. It is claimed that the biphenamine is being dissolved in aloe vera to promote healing of the lesion.
In the management of a wound, one saying to consider is; "Do not put in a wound what you would not put in your own eye."
Desirable characteristics of a wound cleanser include that it must not break down local or systemic defenses, and that it must not interfere with the natural wound healing process. Further, the indications and method of application are also of importance. Thus, in the cleaning of a fresh, heavily contaminated wound, the method of application is more important than the type of solution, whereas the reverse is true in cleansing an already infected wound where the cleanser is an aid in debridement.
It is seen that most of the commercially available wound cleansers are either toxic or not physiologically compatible. Further, many of the rather exotic wound cleansers are rather expensive. The present invention overcomes many of the prior art problems as discussed above.